TW201938109A - Biological marker and method for evaluating mild cognitive impairment based on changes of the blood oxygen concentration of the frontal lobe - Google Patents

Abstract

The invention relates to a biological marker and method for evaluating mild cognitive impairment. The method includes attaching a near-infrared spectroscopy device to a subject's head and performing an external stimulus test on the subject; using the near-infrared spectroscopy device to detect changes of the blood oxygen concentration on the frontal lobe of the subject; and further performing calculation and analysis to generate a result report. Based on changes of the oxygen-containing blood and the hypoxic blood, it is able to evaluate whether the subject has cognitive impairment so as to achieve an effect of early detection and early treatment.

Description

Markers and methods for assessing cognitive dysfunction

The present invention relates to a marker and method for assessing cognitive dysfunction, especially to obtain changes in the concentration of oxygenated blood and hypoxic heme in the brain through a near-infrared device, and analyze whether the patient has cognitive dysfunction through analysis.

With the rapid aging of the current social population structure, the population of dementia is rapidly increasing, and the issues related to dementia have also received much attention. There is currently no cure for dementia. Therefore, the care of dementia has become a challenge. , Not only cause a lot of distress to the family, but also form a burden on society; although there are no drugs that can completely cure dementia, it can still provide drugs for the cause of the disease to delay the deterioration of patients, especially in the early stage of the disease. Therefore, how to detect it in the early stages of dementia has become an important issue in dementia today.

Dementia can be divided into two major types, "Degenerative Dementia" and "Vascular Dementia", which can be distinguished according to the source of brain lesions. The former is due to the degeneration of the neuronal body and the latter is due to the brain. Infarction or bleeding of blood vessels causes brain cells to be damaged or even died due to insufficient blood supply, but these two types of dementia often coexist. In patients who have had a stroke, the cerebral blood circulation is dysfunctional due to a stroke, which results in the death of brain cells and further causes mental retardation. According to statistics, approximately 20%-40% of patients who have had a stroke have a chance of developing dementia within five years. No matter what type of stroke, as long as the number of strokes or the location of the damage is severe enough, it may cause The occurrence of dementia may aggravate its original dementia.

Another study found that due to the damage of cerebral blood vessels in patients with dementia, functional physiological parameters such as vascular perfusion and oxygen metabolism rate have a tendency to decrease compared to healthy populations, and vascular reactivity is regarded as an important factor affecting dementia . In addition, the human prefrontal system is responsible for the judgment of cognitive function and personality, and patients with early cognitive impairment or dementia are likely to find lesions in the brain's microvasculature, and vascular function is more severely damaged in the frontal lobe. As a result, the patient's ability to focus and perform is reduced, so it can be used as a diagnosis to help physicians detect dementia early.

An infrared spectroscopy to monitor changes in tissue oxygen conventional optical technology, the principle is to use optical tissue properties of different materials have different absorption coefficients (μ _a), the change in oxygen to obtain a local tissue. Near-infrared spectroscopy (NIRS) uses a non-invasive optical detection method, which is often used to monitor changes in blood oxygen in the brain tissue and quantify them as functional parameters of the tissue.

Mild Cognitive Impairment (MCI) refers to a disorder of cognitive function between dementia and poor intelligence. Patients generally have no problems in life, but the decline in memory exceeds the normal standard. For clinical screening of mild cognitive dysfunction, scale tests are often used as diagnostic criteria, such as mini-mental state examination (MMSE), Wisconsin card sorting test (WCST), and cognitive function. Obstacle screening scale (CASI) and clinical dementia rating (CDR). These measurement scales are used to test the subject's ability to focus and perform functions. Through external stimuli, they can transform them into decision-making capabilities. The Wisconsin Card Sorting Test is highly sensitive to subjects with “frontal cortex damage”. In addition, the frontal cortex is affected by aging faster than other areas of the brain, so the Wisconsin Card Sorting Test is also Commonly used in studies of brain aging.

Recent studies have pointed out that cognitive function and neurovascular coupling response (NVC response) have a high positive correlation. When nerve activation leads to increased oxygen consumption, the neurovascular coupling response causes blood perfusion in the blood vessels around the nerve. Increase to supplement the oxygen consumption, and its oxygenated blood concentration change will increase during measurement. If the neurovascular coupling response is impaired, cognitive function will be impaired, but the research results show that regardless of whether the subject has cognitive dysfunction, the change in oxygenated blood concentration will increase, so it can not be diagnosed from this. cognitive dysfunction.

The purpose of the present invention is to provide a method for evaluating cognitive dysfunction, which can diagnose whether a patient has cognitive dysfunction through a simple test in a short time.

In order to achieve the above purpose, the technical means lies in the method for assessing cognitive dysfunction, including the following steps:

Step 1: Attach a NIR device to the subject's brain;

Step 2: Require the subject to close their eyes and relax for 1 minute as the baseline value for blood oxygen changes;

Step 3: Test the subject with an external stimulus source;

Step 4: The subject closes his eyes again and relaxes for 2 minutes to complete the test;

Step 5: At the same time as the subject's test, the near-infrared spectroscopy device transmits a blood oxygenation signal of a brain's prefrontal lobe to a computing center for data storage and analysis in real time through a wired or wireless method;

Step 6: Analyze the results. When the oxygenated blood and hypoxic blood concentrations of the left and right prefrontal lobes of the subject both increase, it is assessed as having cognitive dysfunction.

The above-mentioned evaluation method is simple, fast, and time-consuming, and does not require the subject to take too many difficult tests. Moreover, after the subject completes the foregoing steps, the results can be generated immediately, reducing the time when the subject or the tested family waits for results. In the mood, under the rapid diagnosis result of the present invention, the effect of early detection and early treatment can be achieved.

Another object of the present invention is to provide a marker for evaluating cognitive dysfunction, through which the possibility of early detection of the possibility of dementia can be diagnosed through the marker.

In order to achieve the above purpose, the technical means is to detect the subject's blood oxygen change signal in the brain through the near-infrared spectroscopy device when the subject is stimulated. When changes in oxygen blood and hypoxic blood concentrations increase, it indicates that the left and right prefrontal lobes that control cognition are damaged, that is, the subject has cognitive dysfunction.

In order for your review committee to have a further understanding and understanding of the technical means and operation process of the present invention, examples are given in conjunction with the drawings, which are described in detail below.

Example one

This example intends to use a short smart test ("Wisconsin Card Classification Test (WCST)" in this example) as a stimulus to the brain of the subject, and detect the left and right brains of the subject through near-infrared spectroscopy. Changes in prefrontal blood oxygen concentration.

According to the clinical diagnosis and short intelligent test (MMSE, the test score below 25 indicates that the test subject has cognitive dysfunction), the test is divided into the following 4 groups: a control group 1: a non- Subjects with stroke and normal cognitive function, a control group 2: subjects with stroke and normal cognitive function, experimental group 1: subjects without stroke but with cognitive dysfunction, and experimental group 2: with stroke and having Subjects with cognitive impairment.

Please refer to the figures 1 to 3, in this embodiment, a near-infrared spectroscopy device 30 is first attached to the brain of a subject 20, wherein the near-infrared spectroscopy device 30 has a plurality of pairs capable of emitting different near-infrared wavelengths. LED light source 31 and a light sensor 32, the light sources 31 need to face the forehead of the subject 20, that is, the prefrontal part, please refer to the positions of Fq1 and Fq2 shown in Figure 3, and then measure the front left Changes in the blood oxygen concentration of the frontal lobe and the right prefrontal lobe, and a blood oxygen concentration change signal 33 of the brain's prefrontal lobe is generated. The light sensor 32 is used to transmit data to a computing center 40 via a wired or wireless method for data storage and storage. For analysis, the sampling frequency can be set up to 50 Hz.

In this embodiment, three pairs of LED light sources 31 are used, and each pair of LED light sources 31 can emit two kinds of near-infrared light with different wavelengths. In human tissues, light in the 650nm to 950nm band mainly absorbs light from blood. Oxyheme and hypoxia heme, so this embodiment uses light in the 760 nm and 850 nm bands, respectively, and the distance between the three pairs of LED light sources 31 and the light sensor 32 is 30 mm and 35 mm from the inside to the outside respectively. , 40 mm.

The quiz process is divided into three stages:

1. Rest period: The subject 20 is required to close his eyes and relax for 1 minute as the baseline value of blood oxygen change.

2. Test phase: A test of the stimulus source 10 is performed on the test subject 20, and the test time varies depending on the test subject and the stimulus source.

3. Recovery stage: The subject 20 closed his eyes again and relaxed for 2 minutes to complete the test.

The value of the change in blood oxygen concentration in the 20 test of each subject is the blood oxygen concentration value in the test phase minus the blood oxygen concentration value in the rest phase, and the blood oxygen concentration changes in the left and right frontal lobe are recorded separately.

Please refer to Figure 4. Regardless of whether the subject has had a stroke or has cognitive impairment, the change in oxygenated blood concentration will increase.

Please refer to Figure 5. Subjects with normal cognitive function (control group 1), although the oxygen consumption increased when the brain was stimulated, but the blood supply also increased, so the hypoxic blood concentration changed. Regardless of the left and right prefrontal lobe, the changes of hypoxemia blood level decreased; while subjects with cognitive impairment, such as the experimental group 1, 2, the changes of hypoxic blood concentration increased regardless of the left and right prefrontal lobe. This shows that, although people with cognitive impairment have increased oxygen consumption when the brain is stimulated, the hypoxic blood concentration in the prefrontal lobe will increase due to insufficiency due to increased blood supply.

Please refer to FIG. 5 again. The results in control group 2 further confirm that if the changes in left and right prefrontal hypoxic blood concentrations increase, it is an indicator for judging whether the subject has cognitive dysfunction; the control group in FIG. 5 2 is a subject who has had a stroke but whose cognition is normal in a short smart test. Because the patient's brain was damaged when the stroke occurred, it is impossible to determine from the appearance whether the left prefrontal or right prefrontal lobe is damaged. In the example, the left prefrontal hypoxic blood concentration of the control group 2 increased, showing that the function of increasing the left prefrontal blood flow supply has been impaired, but the right prefrontal hypoxic blood concentration changed normally, indicating that the subject can still pass through the right front Frontal thinking and identification, so the results of the short intelligent test showed that these subjects did not have cognitive impairment.

Further, this device can be used to evaluate the changes in the oxygenated blood concentration and hypoxic blood concentration of the left and right prefrontal lobes of the subject after stimulation, and various parameters derived therefrom, as a diagnostic indicator of whether the subject has cognitive dysfunction. To achieve early detection and early treatment.

Example two

Please refer to FIG. 1 to FIG. 3. A marker and method for evaluating cognitive dysfunction according to the present invention include: the stimulus source 10, the near-infrared spectroscopy device 30, and receiving signals from the near-infrared spectroscopy device 30 and generating The result is the arithmetic unit 40.

Methods to assess cognitive dysfunction include:

Step 1: Attach the near-infrared spectroscopy device 30 to the head of the subject 20;

Step 2: The subject 20 is subjected to the stimulus source 10 test for cognitive dysfunction test. In this embodiment, the Wisconsin card sorting test (WCST) is used. At this time, the near-infrared spectroscopy device 30 performs Detection of the blood oxygen concentration change in the prefrontal lobe of the brain of the subject 20, and generating a blood oxygen change signal 33 in the prefrontal lobe of the brain;

Step 3: The arithmetic unit 40 receives the blood oxygen change signal 33 detected by the near-infrared spectroscopy device 30, and quantifies the signal as a result report 50 according to changes in oxygenated blood and hypoxic blood concentration, respectively; and

Step 4: The results report that the oxygenated blood concentration change in 50 is the control group. When the oxygenated blood concentration of the subject rises, it indicates that the operation is normal, and then the changes in hypoxic blood concentration are interpreted. The changes in oxygen and blood concentration all increase, that is to say, the subject is judged to have cognitive dysfunction (see Figures 4 and 5), which can be further diagnosed with the results of the cognitive test.

However, the above are only the preferred embodiments of the present invention, and the scope of implementation of the present invention cannot be limited by this; therefore, any simple equivalent changes and modifications made in accordance with the scope of the patent application and the contents of the invention specification of the present invention , All should still fall within the scope of the invention patent.

10‧‧‧ Stimulus

20‧‧‧ Subject

30‧‧‧Near infrared spectrometer

31‧‧‧LED light source

32‧‧‧light sensor

33‧‧‧ blood oxygen change signal

40‧‧‧ Computing Unit

50‧‧‧ Results report

Figure 1 is a schematic diagram of the operation of the present invention.

FIG. 2 is a schematic diagram of a near-infrared spectroscopy device of the present invention.

FIG. 3 is a schematic diagram of the attachment position of the near-infrared spectroscopy device of the present invention.

Figure 4 is the result of oxygenated blood changes in the present invention.

Figure 5 shows the results of hypoxic blood changes according to the present invention.

Claims (10)

A method for assessing cognitive dysfunction includes the following steps: Step 1: Attach a near-infrared spectroscopy device to the subject's head to detect the blood oxygen concentration in the prefrontal lobe of the subject's brain; Step 2 : Require the subject to relax as a baseline value for changes in blood oxygen concentration; Step 3: Let the subject perform a test, that is, to give a stimulus to the brain; Step 4: Ask the subject to relax again after the test The near-infrared spectroscopy device transmits the detected signal of blood oxygen changes in the prefrontal brain of the brain to an operation center during the whole process; and step 5: the operation unit analyzes changes in oxygenated blood concentration of the left and right brain frontal leaves and Hypoxic blood concentration changes and a result report is generated to assess whether the subject has cognitive impairment. The method for assessing cognitive dysfunction as described in item 1 of the scope of patent application, wherein the assessment method is an increase in the oxygenated blood concentration of the left and right prefrontal lobe and the hypoxia of the left and right prefrontal lobe in the result report. The rise in blood concentration means that the subject has cognitive impairment. The method for assessing cognitive dysfunction as described in item 1 of the scope of patent application, wherein the near-infrared spectroscopy device has a plurality of pairs of LED light sources capable of emitting different near-infrared wavelengths and a light sensor, and these LED light sources use Infrared can detect changes in the concentration of oxygenated blood and hypoxic blood in the brain tissue and transmit it to the computing center. The method for assessing cognitive dysfunction described in item 3 of the scope of patent application, wherein each pair of these LED light sources can emit two kinds of near-infrared light with different wavelengths, which are 760 nm and 850 nm, respectively. According to the method for assessing cognitive dysfunction described in item 4 of the scope of patent application, the distance between the three pairs of LED light sources and the light sensor is 30 mm, 35 mm, and 40 mm from the inside to the outside, respectively. A marker used to evaluate cognitive dysfunction, which is a change in the oxygenated blood and hypoxic blood concentrations of a subject's left and right prefrontal lobes before and after stimulation of the brain, which is a marker to determine that the subject has cognitive dysfunction. . The marker for assessing cognitive dysfunction as described in item 6 of the scope of patent application, wherein the marker is detected through the following steps: Step 1: Attach a near-infrared spectroscopy device to the subject's head to perform the test Detection of blood oxygen concentration in the frontal lobe of the subject's brain; Step 2: Ask the subject to relax as a reference value for changes in blood oxygen concentration; Step 3: Let the subject perform a test, which is to give a stimulation to the brain Step 4: After the test, ask the subject to relax again, and the near-infrared spectroscopy device transmits the detected signal of blood oxygen changes in the prefrontal lobe of the brain to a computing center during the whole process; and Step 5: The arithmetic unit analyzes changes in oxygenated blood concentration and hypoxic blood concentration in the left and right prefrontal lobes, and generates a result report with a marker for evaluating cognitive dysfunction to evaluate whether the subject has cognitive dysfunction. The marker for assessing cognitive dysfunction as described in item 7 of the scope of patent application, wherein the near-infrared spectroscopy device has a plurality of pairs of LED light sources capable of emitting different near-infrared wavelengths and a light sensor, and these LED light sources use Infrared can detect changes in the concentration of oxygenated blood and hypoxic blood in the brain tissue and transmit it to the computing unit. According to the marker for evaluating cognitive dysfunction described in item 8 of the scope of patent application, each pair of these LED light sources can emit two kinds of near-infrared light with different wavelengths, which are 760 nm and 850 nm, respectively. According to the mark for assessing cognitive dysfunction described in item 9 of the scope of patent application, the distance between the three pairs of LED light sources and the light sensor is 30 mm, 35 mm, and 40 mm from the inside to the outside, respectively.